Probing the Relationship Between the Human Gut Microbiome and Prospects of Prostate Cancer: A Systematic Review.

Prostate neoplasia is one of the most commonly occurring neoplasias in males and has a high mortality rate. Prostate cancer (PCA) risk factors include tall stature, male sex, known family history, obesity, high blood pressure, lack of fitness, higher levels of testosterone for a long time, increasing age, and ethnicity are well known. The association and role of the gut microbiota in different diseases in our body have been highlighted recently. Therefore, finding the influence of gut microbiota on the prostatic cells can be useful for preventing prostatic neoplasia and/or reducing its severity. We aimed to assess its impact on PCA risk. We thoroughly searched databases for the relevant literature for our systematic review. The final research papers analyzed how bacteria played a role in the risk of PCA, either through inflammation or the production of metabolites that increase/decrease the risk of PCA. Based on the studies reviewed, we found that some gut bacteria play a role in the formation of PCA. In contrast, some bacteria can help prevent PCA, but the metabolism of the dietary components is the major factor for PCA.

Hidden clues in prostate cancer - Lessons learned from clinical and pre-clinical approaches on diagnosis and risk stratification.

The heterogeneity of prostate cancer is evident at clinical, morphological and molecular levels. To aid clinical decision making, a three-tiered system for risk stratification is used to designate low-, intermediate-, and high-risk of disease progression. Intermediate-risk prostate cancers are the most frequently diagnosed, and even with common diagnostic features, can exhibit vastly different clinical progression. Thus, improved risk stratification methods are needed to better predict patient outcomes. Here, we provide an overview of the improvements in diagnosis/prognosis arising from advances in pathology reporting of prostate cancer, which can improve risk stratification, especially for patients with intermediate-risk disease. This review discusses updates to pathology reporting of morphological growth patterns, and proposes the utility of integrating prognostic biomarkers or innovative imaging techniques to enhance clinical decision-making. To complement clinical studies, experimental approaches using patient-derived tumors have highlighted important cellular and morphological features associated with aggressive disease that may impact treatment response. The intersection of urology, pathology and scientific disciplines is required to work towards a common goal of understanding disease pathogenesis, improving the stratification of patients with intermediate-risk disease and subsequently defining optimal treatment strategies using precision-based approaches.

Neuroendocrine cells in prostate cancer correlate with poor outcomes: a systematic review and meta-analysis.

OBJECTIVES: To perform a systematic review and meta-analysis of the literature to understand the variation in the reporting of neuroendocrine staining and determine the influence of reporting neuroendocrine staining at diagnosis on patient outcomes. METHODS: Medical databases were searched to identify studies in which adenocarcinoma specimens were stained with any of the following four neuroendocrine markers: chromogranin A (CgA), neuron-specific enolase (NSE), synaptophysin and CD56. The prevalence of neuroendocrine staining and correlation of the prevalence of neuroendocrine staining to patient outcomes were analysed using a random-effects model. All statistical tests were two-sided. RESULTS: Sixty-two studies spanning 7616 patients were analysed. The pooled prevalence for the most common marker, CgA (41%), was similar to that of NSE (39%) and higher than that of synaptophysin (31%). The prevalence of CgA staining was significantly influenced by reporting criteria, where objective thresholds reduced the variation in prevalence to 26%. No correlation was found between CgA prevalence and tumour grade. Patients positive for CgA staining using objective criteria had more rapid biochemical progression (hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.49 to 2.65) and poorer prostate cancer-specific survival (HR 7.03, 95% CI 2.55 to 19.39) compared to negative patients, even among those with low-risk cancers. CONCLUSION: Discrepancies in the reported prevalence of neuroendocrine cells in adenocarcinoma are driven by the inconsistent scoring criteria. This study unequivocally demonstrates that when neuroendocrine cell staining is assessed with objective criteria it identifies patients with poor clinical outcomes. Future studies are needed to determine the exact quantifiable thresholds for use in reporting neuroendocrine cell staining to identify patients at higher risk of progression.

Vínculos entre psicooncología y enfermería en el cuidado continuo de personas con cáncer de próstata / Links between Psycho-Oncology and Nursing in the Ongoing Care of Individuals with Prostate Cancer

Introducción: La enfermería en oncología ocupa un lugar preponderante dentro del equipo multidisciplinar, y el concepto de cuidado va más allá de actividades técnicas, donde toda relación terapéutica implica, de modo necesario, un proceso de relación interpersonal, para lo cual se deben desarrollar habilidades y destrezas comunicativas. Objetivo: Analizar los vínculos entre la psicooncología y la enfermería en el cuidado continuo de personas con cáncer de próstata. Métodos: Revisión bibliográfica sistemática de artículos publicados desde 2011 hasta 2020 en las bases de datos SciELO, Google académico y Dialnet. Se elaboró la pregunta guía a través del acrónimo PICo. La estrategia de búsqueda se realizó mediante los descriptores en Ciencias de la Salud (DeCS) "Psicooncología", "Enfermería", "Cuidados continuos", "Neoplasia de la próstata" y "Enfermedades crónicas" con los operadores booleanos AND y OR. Se utilizó el diagrama de flujo (PRISMA). Se accedió a interpretar los referentes teóricos y organización del conocimiento en las 16 bibliografías seleccionadas. Conclusiones: La revisión realizada permitió enfatizar la importancia de integrar técnicas y habilidades de la psicooncología, sus beneficios y aplicación desde las perspectivas de enfermería, con el propósito de favorecer el bienestar biopsicosocial de la persona con cáncer de próstata(AU)

Introduction: Nursing in oncology occupies a preponderant place within the multidisciplinary team, and the concept of care goes beyond technical activities, any therapeutic relationship necessarily implies an interpersonal relationship process, for which skills and communication skills must be developed. Objective: To analyze the links between psycho-oncology and nursing in the continuous care of individuals with prostate cancer. Methods: We develop a systematic bibliographic review of articles published from 2011 to 2020 in the SciELO, Google academic and Dialnet databases. The guiding question was developed through the acronym PICo. The search strategy was carried out using the Health Sciences (DeCS) descriptors "Psychooncology", "Nursing", "Continuous care", "Prostate neoplasia" and "Chronic diseases" with the Boolean operators AND and OR. PRISMA flow chart was used. It was agreed to interpret the theoretical references and organization of knowledge in the 16 selected bibliographies. Conclusions: The review carried out made it possible to emphasize the importance of integrating techniques and skills of psycho-oncology, their benefits and application from the nursing perspectives, with the purpose of favoring the bio psychosocial well-being of the person with prostate cancer(AU)

Personalized Medicine for Prostate Cancer: Is Targeting Metabolism a Reality?

Prostate cancer invokes major shifts in gene transcription and metabolic signaling to mediate alterations in nutrient acquisition and metabolic substrate selection when compared to normal tissues. Exploiting such metabolic reprogramming is proposed to enable the development of targeted therapies for prostate cancer, yet there are several challenges to overcome before this becomes a reality. Herein, we outline the role of several nutrients known to contribute to prostate tumorigenesis, including fatty acids, glucose, lactate and glutamine, and discuss the major factors contributing to variability in prostate cancer metabolism, including cellular heterogeneity, genetic drivers and mutations, as well as complexity in the tumor microenvironment. The review draws from original studies employing immortalized prostate cancer cells, as well as more complex experimental models, including animals and humans, that more accurately reflect the complexity of the in vivo tumor microenvironment. In synthesizing this information, we consider the feasibility and potential limitations of implementing metabolic therapies for prostate cancer management.

Association between TMPRSS2:ERG fusion gene and the prostate cancer: systematic review and meta-analysis.

INTRODUCTION: To identify the association between the TMPRSS2:ERG fusion gene, their variants and the onset of localized prostate cancer. MATERIAL AND METHODS: A systematic search strategy was carried out through MEDLINE, EMBASE, LILACS, CENTRAL and unpublished literature. We included randomized control trials, cohort, case-control and cross-sectional studies that involved patients >18 years-old assessing the association between TMPRSS2 fusion gene, its single nucleotide polymorphisms and prostate cancer. The primary outcome was prostate cancer defined by histology of the tumor coming from transrectal ultrasound guided biopsy, transurethral resection of the prostate or radical prostatectomy. We assessed the risk of bias with QUADAS2 and performed a meta-analysis with Stata 14. RESULTS: We found 241 records with the search strategies. After duplicates were removed, 18 studies were included in qualitative analysis and 15 studies in meta-analysis. All included studies that had no applicability concerns and low risk of bias for flow and timing. Nine studies had an unclear risk of bias for index and reference tests, since they did not describe the blinding assessment appropriately. Regarding the association between TMPRSS2:ERG and prostate cancer, we found an odds ratio (OR) 2.24 and a 95% confidence interval (CI) (1.29 to 3.91). Regarding the kind of sample, urine showed an OR 2.79 and a 95% CI (1.12 to 6.98) and when using a DNA molecular template, the OR was 3.55 with a 95% CI (1.08 to 11.65). CONCLUSIONS: There was an association between TMPRSS2:ERG fusion gene with the diagnosis of prostate cancer, mainly in urine samples and DNA-based molecular templates. TMPRSS2:ERG might be used as the gold standard biomarker for diagnosis and stratification of PCa.

Avaliação de margens circunferenciais, extensão extraprostática e escore de Gleason em produtos de prostatectomia radical examinados por método de inclusão parcial e método de inclusão parcial com inclusão suplementar de toda periferia da próstata / Evaluation of circumferential margins, extraprostatic extension and Gleason score in radical prostatectomy products examined by partial inclusion method and partial inclusion method with supplementary inclusion of all periphery of the prostate

INTRODUÇÃO: Estudos recentes sugerem que a inclusão parcial deixa de detectar até 21% e 47% de margens circunferenciais positivas (MCP) e extensão extraprostática (EEP),respectivamente. Kim et al (2009) sugerem que a inclusão de toda a periferia da próstata (3mm de espessura) previne a falha na detecção de MCP e EEP. OBJETIVO: Comparar um método de inclusão parcial de produtos de prostatectomia radical com a inclusão suplementar de toda periferia da próstata. METODOLOGIA: Foram revistos 148 casos de produtos de prostatectomia radical em dois serviços de patologia de Salvador-BA, após a adoção de um protocolo incluindo 3mm de tecido periférico da próstata. Foi avaliado se após a análise das lâminas histológicas adicionais houve mudança na margem, extensão extraprostática,escore de Gleason e extensão da MCP e EEP. RESULTADOS: O método de inclusão parcial deixou de detectar 29% do envolvimento de MCP e 20% dos casos com EEP. Mudança de acometimento focal para extenso foi observada em 11/21 (52%) casos de MCP e em 5/13 (38%) dos casos de EEP. Mudança no escore de Gleason foi incomum (5%). CONCLUSÃO:Os resultados mostram a importância da inclusão de toda a periferia da próstata para análise microscópica quando métodos de inclusão parcial são adotados.

BACKGROUND: Recent data suggest that up to 21% of positive circumferential margins (PCM) and 47% of extraprostatic extension (EPE) samples may be missed when partial embedding methods are employed. Kim and colleagues (2009) suggested that total inclusion of the periphery (3 mm rim) of the prostate prevented the failure to detect PCM and EPE. DESIGN: Radical prostatectomy specimen (n = 148) slides were reviewed after adoption of a protocol that included a 3 mm rim of peripheral tissues. We evaluated whether the analysis of supplemental slides of prostate periphery changed margin status, presence of EPE, Gleason score and extent of PCM and EPE. RESULTS: Partial sampling resulted in missing 29% of PCM and 20% of EPE without using data from the supplemental slides of prostate periphery. Changes from focal to extensive disease were found in 11/21 (52%) cases of positive circumferential margins and in 5/13 (38%) cases of extraprostatic extension. Changes in the Gleason score were uncommon (5%). CONCLUSIONS: These results indicate the importance of including all the prostate peripheral tissue for microscopic analysis when partial embedding methods are adopted.

The risk of prostate cancer for men on aspirin, statin or antidiabetic medications.

BACKGROUND: A decreased risk of prostate cancer (PCa) has been suggested in men taking aspirin, statins and metformin, although the evidence has been conflicting. We estimated the association between prescribed medications, prostate specific antigen (PSA) levels and the risk of either any PCa or high-grade PCa. METHODS: This population-based cohort study included 185,667 men having a first recorded PSA test and 18,574 men having a first prostate biopsy in Stockholm County, Sweden for the period 2007-2012. Detailed clinical information including PSA levels, biopsy results, comorbidities and educational level were obtained from population-based registers. High-grade prostate cancer was defined as a Gleason score of seven or higher. Differences in PSA levels by medication status were estimated using linear regression on log PSA values. PCa risk was estimated using multivariate logistic regression. RESULTS: Compared with men who were not on medication, the PSA level at the first PSA test was lower among men using 75 mg/dose aspirin (-3.9% change in PSA concentration; 95% confidence interval (CI): -5.8 to -2.1), statin (-4.6%; 95% CI: -6.2 to -2.9), metformin (-14%; 95% CI: -17 to -12) and insulin (-16%; 95% CI: -18 to -14). Men using any statins had an increased risk of both high-grade PCa (odds ratio (OR) 1.25; 95% CI: 1.10-1.42) and PCa of any grade (OR 1.16; 95% CI 1.04-1.29). There were no significant associations between aspirin or any antidiabetic medication and the risk of PCa. CONCLUSION: We found no protective effect of aspirin, statins or antidiabetics in terms of risk for any PCa or high-grade PCa. Use of any statins was associated with an elevated risk of being diagnosed with high-grade prostate cancer.

Novel In Vivo model for combinatorial fluorescence labeling in mouse prostate.

BACKGROUND: The epithelial layer of prostate glands contains several types of cells, including luminal and basal cells. Yet there is paucity of animal models to study the cellular origin of normal or neoplastic development in the prostate to facilitate the treatment of heterogenous prostate diseases by targeting individual cell lineages. METHODS: We developed a mouse model that expresses different types of fluorescent proteins (XFPs) specifically in prostatic cells. Using an in vivo stochastic fluorescent protein combinatorial strategy, XFP signals were expressed specifically in prostate of Protein Kinase D1 (PKD1) knock-out, K-Ras(G) (12) (D) knock-in, and Phosphatase and tensin homolog (PTEN) and PKD1 double knock-out mice under the control of PB-Cre promoter. RESULTS: In vivo XFP signals were observed in prostate of PKD1 knock-out, K-Ras(G) (12) (D) knock-in, and PTEN PKD1 double knock-out mice, which developed normal, hyperplastic, and neoplastic prostate, respectively. The patchy expression pattern of XFPs in neoplasia tissue indicated the clonal origin of cancer cells in the prostate. CONCLUSIONS: The transgenic mouse models demonstrate combinatorial fluorescent protein expression in normal and cancerous prostatic tissues. This novel prostate-specific fluorescent labeled mouse model, which we named Prorainbow, could be useful in studying benign and malignant pathology of prostate.

The meaning of touch the prostate for man: the nurse in health promotion / O significado do toque da próstata para o homem: enfermeiro na promoção da saúde / El sentido del tacto de la próstata para el hombre: enfermero en la promoción de la salud

Objetivos: Identificar o significado para os homens sobre o exame clínico de toque digital da próstata para detecção precoce de câncer, caracterizar a causa do déficit na procura de exame preventivos e serviços de saúde pelos homens e discutir atuação do enfermeiro na promoção da saúde dos homens. Método: Estudo qualitativo descritivo com pesquisa de campo norteada por formulário semi-estruturado. Resultados: Os significados atribuídos ao toque digital da próstata foram constrangimento, desconforto, estigma e importante. A informação e o acesso estão condicionados aos fatores socioeconômicos dos participantes. Conclusão: Enfermeiros devem assistir na educação em saúde e na saúde integral, uniformizando as informações para diferentes grupos socioeconômicos, minimizando o estigma e o constrangimento, ressaltando a importância do autocuidado para o homem, visando melhorar a busca pelos serviços de saúde, exames de rastreamento e prevenção.

Objectives: To identify the meaning for the men on the clinical examination of digital touch Prostate cancer early detection, to characterize the cause of the deficit in the search for preventive examination and health services by men and discuss the nurse's role in promoting men's health. Method: Qualitative descriptive study with field research guided by semi-structured form. Results: The meanings attributed to the digital touch of the prostate were embarrassment, discomfort, stigma and important. The information and access are tied to socioeconomic factors of the participants. Conclusion: Nurses should assist in health education and comprehensive health care by standardizing the information for different socioeconomic groups, minimizing the stigma and embarrassments, highlighting the importance of self care for man, to improve the search for health services, screening exams and prevention.

Objetivos: Identificar el significado de los hombres en el tacto digital de detección de cáncer de próstata, caracterizar la causa del déficit en la búsqueda de examen y los servicios preventivos de salud por los hombres y discutir el papel de la enfermera en la promoción de la salud masculina. Método: investigación cualitativa descriptiva de campo guiada por formulario séme-estructurado. Resultados: Los significados atribuidos al tacto digital de la próstata son vergüenza, incomodidad, estigma y importante. La información y acceso están condicionados a factores socioeconómicos de los participantes. Conclusión: Enfermeras deben asistir en la educación en salud y la salud integral, mediante la estandarización de la información para los diferentes grupos socioeconómicos, minimizando el estigma y la vergüenza, resaltando la importancia del auto cuidado para el hombre, para mejorar la búsqueda de los servicios de salud, exámenes de rastreo y prevención.

Radioterapia conformada en pacientes con cáncer de próstata. Experiencia de tres años en el Instituto Nacional de Cancerología de Colombia / Conformal Radiotherapy in Patients with Prostate Cancer A Three-Year Study at the National Cancer Institute of Colombia

Objetivo: Describir las características clínicas y demográficas y la supervivencia libre de cualquier evento y toxicidad en pacientes con cáncer localizado de próstata, tratados con radioterapia conformada en el Instituto Nacional de Cancerología. Métodos: Se revisaron los registros de pacientes tratados con radioterapia conformada entre enero del 2003 y diciembre del 2006. Se realizaron análisis descriptivos y se analizó la supervivencia mediante el método de Kaplan-Meier. Resultados: Se trataron 196 pacientes y se incluyeron 114 en el análisis. La mediana de seguimiento fue de 14,4 meses. La supervivencia libre de enfermedad, a 30 meses, fue de 74%. Se presentaron seis eventos en el grupo de alto riesgo y tres en el de riesgo intermedio; no se presentaron eventos en el de bajo riesgo. La supervivencia libre de recaída fue de 100%, 73% y 63% para los riesgos bajo, intermedio y alto, respectivamente. La toxicidad crónica urinaria no preexistente de cualquier grado fue de 12,8%; la rectal, de 10,8%, y la sexual, de 18,3%. Conclusiones: El seguimiento fue corto y limita la posibilidad de hacer comparaciones con series internacionales. No se demostraron diferencias estadísticamente significativas en la supervivencia libre de recaída, según grupos de riesgo; sin embargo, los eventos se presentaron acordes con el riesgo. Un tamaño de muestra superior podría haber incrementado la potencia del estudio para detectar estas diferencias. La toxicidad rectal, sexual y urinaria no se midió de manera sistemática, por lo cual los resultados no son concluyentes. Se deben implementar guías para definir el manejo con hormonoterapia.

Objective: To describe clinical and demographic characteristics, event free survival, and the toxicity in prostate cancer patients treated with conformal radiotherapy at the National Cancer Institute of Colombia. Methods: Case histories of patients treated with conformal radiotherapy between January, 2003 and December, 2006 were reviewed. Descriptive analyses were carried out and a survival analysis was performed with the Kaplan-Meier method. Results: One hundred and ninety-six patients were treated, 114 of whom were included in the analyses. Median follow-up was 14.4 months. Disease free survival at month 30 was 74%. Six events occurred in the high risk group, three in the intermediate risk group, and none in the low risk group. Relapse free survival was 100%, 73% and 67% for the low, intermediate, and high risk groups, respectively. Non pre-existent chronic toxicity of any degree was: 12.8%, urinary; 10.8%, rectal; and 18.3%, sexual. Conclusions: Follow-up was short and the possiblity of making comparisons with international series was limited. According to risk group, no statistically significant differences were shown for relapse free survival; however, events occurred in accordance with level of risk. A larger sample group could have enhanced the study´s potential to detect these differences. Rectal, sexual and urinary toxicities were not measured systematically, hence the results are not conclusive. Guidelines should be adopted for the application of hormonotherapy.

Avaliação do valor da relação do antígeno prostático específico livre e total no diagnóstico do câncer de próstata / Evaluation of the value of the relation between free and total prostate-specific antigen in the diagnosis of prostate cancer

Introdução: Este estudo visa a determinar a importância da relação PSA livre (PSAL) / PSA total (PSA) como forma de diferenciar câncer de próstata (CAP) de hiperplasia prostática benigna (HPB) em homens com níveis séricos de PSA entre 4,1 e 10 ng/ml. Material e métodos: Entre 1999 e 2000, 140 homens consecutivos com PSA entre 4,1 e 10 ng/ml foram submetidos à biópsia prostática. Utilizou-se como ponto de corte uma RLT de 0,16, sendo valores iguais ou inferiores a este considerados sugestivos de CAP. Resultados: Em 42 homens (30%) foi detectado CAP e em 98 (70%), HPB. Entre os homens com CAP, 31 (74%) apresentaram RLT igual ou inferior a 0,16 e 11 (26%) apresentaram-na superior a este valor. Entre os homens com HPB, 25 (25,5%) apresentaram RLT igual ou inferior a 0,16 e 73 (74,5%) apresentaram-na superior a este valor. A razão de chance de CAP para os homens com RLT igual ou inferior a 0,16 foi de 8,23 (IC 95%, 3,61 ­ 18,76). A sensibilidade da RLT na detecção do CAP foi de 73,8% e a especificidade de 74,5%. Os valores preditivos positivo e negativo foram 55,4% e 86,9%, respectivamente. Conclusão: O ponto de corte igual ou inferior a 0,16 para a RLT pode ser utilizado como critério auxiliar para enfatizar indicação de biópsia prostática em homens com PSA entre 4,1 e 10 ng/ml, pelo fato de este grupo apresentar um risco maior de CAP. Entretanto, não deve ser utilizado para contra-indicar a biópsia prostática, pela possibilidade de falha diganóstica e não detecção de casos de CAP (AU)

Introduction: The aim of this study was to evaluate the value of the relation of free PSA / to total PSA (PSA) in the differentiation of prostate cancer from benign prostatic hyperplasia (BPH) in men with PSA levels between 4.1 and 10 ng/ml. Material and Methods: Between 1999 and 2000, 140 consecutive men with PSA levels between 4.1 and 10 ng/ml were submitted to at least one transrectal ultrasound prostate biopsy. Free PSA was measured in all men, and its relation with PSA (FTR) was calculated. A FTR cutoff of 0.16 was used, and men with values at or below it were considered at risk for prostate cancer. Results: Prostate cancer was found in 42 men (30%) and BPH in 98 (70%). Of the men with prostate cancer, 31 (74%) presented with a FTR equal or below 0.16 and 11 (26%) presented with a FTR above this value. The odds ratio (OR) for prostate cancer was 8.23 (CI 95%, 3.61 ­ 18.76) in men with a FTR equal or below 0.16. FTR had a sensibility of 73.8% and a specificity of 74.5% in the detection of prostate cancer. The positive and the negative predictive values were 55.4% and 86.9%, respectively. Conclusion: The cutoff value equal or below 0.16 for the FTR may be used as an auxiliary criteria to emphasize prostate biopsy indication in men with PSA values between 4.1 and 10 ng/ml, since this group is at greater risk of harbouring prostate cancer. Nevertheless, it should not be used to contraindicate prostate biopsy because of the possibility of missing prostate cancer cases (AU)